This proposal is in response to the request (RFA NIAMDD 81-01) for participants with the NIAMDD under cooperative agreements in a multicenter collaborative clinical trial to determine whether strict control of blood glucose concentration is effective in preventing or ameliorating the vascular complications of insulin-dependent diabetes mellitus. The intent of this application is to provide evidence that the University of Tennessee Center for the Health Sciences (UTCHS) has adequate facilities and resources to participate in all four phases of the proposed clinical trial. The investigators at UTCHS have the interest, experience, sufficient patient resources, and desire to undertake this long-term collaborative research endeavor. This application also includes a description of a proposed research design for conduction of Phase II of the multicenter collaborative clinical trial, but it is understood that one of the objectives of Phase I is the development of an acceptable research design through the cooperative efforts of investigators from all centers participating in the trial. The multicenter clinical trial intends to determine: (a) whether a strict control treatment regimen can be used in a group of insulin-dependent diabetic patients to establish and maintain blood glucose control that differs significantly both clinically and statistically from that achieved in a similar group receiving conventional treatment in the same clinical setting; (b) whether these methods of therapy can be applied safely and effectively in a randomized fashion to a population of insulin-dependent diabetics; (c) whether a sufficiently high rate of patient acceptance can be achieved with this therapy; and (d) whether the effect of these therapies on selected biochemical and pathological end points can be adequately and reliably assessed. The objectives of the multicenter clinical trial are fully understood and appreciated by the investigators at UTCHS. They have already sought support to conduct similar investigations. Sources of patients have been established and their physicians are ready to cooperate in efforts to reach the objectives of the study.